NEW YORK, Aug 4 — Scientists say they may have found a sort of magic ingredient to prevent asthma in children: Microbes from farm animals, carried into the home in dust.
The results of their research, published yesterday in The New England Journal of Medicine, were so convincing that they raised the possibility of developing a spray to do the same thing for children who do not have regular contact with cows and horses.
It is a pressing problem because as many as 10.6 per cent of grade-school children have asthma, according to data from the Centres for Disease Control and Prevention. And there is no cure for this chronic and frightening disease.
The discovery originated with an idea that been around for years: That a growing number of children were developing asthma because their daily environments were simply too clean.
If children are exposed to microbes that stimulate their immune systems in the first few years of life, they will be protected against asthma, the hypothesis says. As asthma rates climbed, researchers published study after study supporting what has become known as the hygiene hypothesis.
The most consistent findings were from studies that compared children who grew up on farms — less asthma — with children who grew up in other environments.
But in every case, there were many other differences between the children who had less asthma and those who had more. So it was not clear what exactly might have led to different asthma rates.
What was missing was evidence that one essential factor in the environment was protecting children. And what was needed was a reason it had exerted its effect. The new study provides this, asthma researchers say, which is what makes its results so spectacular.
It is still early. The study was small, and even though its results were striking, more work needs to be done. But, Dr Brian Christman, an immunologist at Vanderbilt University and a volunteer spokesman for the American Lung Association, said, “They really nailed it.”
The new work began when a group of investigators noticed that something peculiar was happening with children from two insular farming groups: The Amish of Indiana and the Hutterites of North Dakota. Asthma is rare among the Amish, affecting 2 to 4 per cent of the population, but common among the Hutterites, with 15-20 per cent affected.
Yet the Amish and the Hutterites have similar genetic backgrounds. The Amish originated in Switzerland, the Hutterites in Austria. Members of both groups have large families and a simple lifestyle. Their diets are similar, children in both groups have little exposure to tobacco smoke or polluted air, and both groups forbid indoor pets. Both groups also have meticulously clean homes.
There was one difference, though: Farming methods. The Amish live on single-family dairy farms. They do not use electricity, and use horses to pull their plows and for transportation. Their barns are close to their homes, and their children play in them. The Hutterites have no objection to electricity and live on large, industrialised communal farms. Their cows are housed in huge barns, more like hangars, away from their homes. Children do not generally play in Hutterite barns.
The researchers decided to start with a small study. They looked at 30 Amish children and 30 Hutterite children and asked what sort of immune cells were in their blood.
“We never thought we would see a difference,” said Carole Ober, an author of the study and the chairwoman of the department of human genetics at the University of Chicago. To the researchers’ astonishment, she said, “we saw whopping differences with very, very different cell types and cell numbers.”
None of the Amish children had asthma. And they all had a large proportion of neutrophils — white blood cells that are the immune system’s paramedics and are part of what is known as the innate immune system. These children’s neutrophils were newly emerged from their bone marrow, evidence of a continual low-grade reaction to microbial invaders.
“All 30 of the Amish kids had this,” said Anne I. Sperling, another author of the study and an associate professor of immunology and medicine at the University of Chicago.
By contrast, six of the 30 Hutterite children had asthma, and all of them had far fewer neutrophils in their blood. The neutrophils that they did have were older ones, not cells that had just emerged. Instead, their blood was swarming with another type of immune cell, eosinophils, which provoke allergic reactions. It was as if they were primed for an asthma attack as soon as they breathed something to set it off.
With the Amish children, Sperling said, it would clearly take a lot more provocation to set off an allergic response.
The researchers decided that the differences between the Amish and the Hutterite children were so great that they should forge ahead with additional research to try to figure out what was stimulating the Amish innate immune system.
They analysed dust from the Amish and the Hutterite homes. The Amish dust was loaded with debris from bacteria; the Hutterite dust was not. The researchers sent the dust to Dr Donata Vercelli, an associate director of the asthma and airway research centre at the University of Arizona, who would test the dust in mice.
She put dust — Amish or Hutterite — into the airways of mice 14 times over a month and then exposed the animals to allergens. She measured how the airways responded: Did they constrict and twitch? Were they inflamed?
“We found exactly what we found in the children,” Vercelli said. “If we give the Amish dust, we protect the mice. If we give the Hutterite dust, we do not protect them.”
Ober and her colleagues heard the results in a conference call with Sperling.
“Our jaws were hanging open,” Ober said. “We could not believe it.”
Vercelli repeated the test and added another control. She gave the Amish dust to mice that were missing genes needed for the innate immune response. This time, the dust did not protect them.
“It was incredibly exciting,” Sperling said. “Now we have a model that allows us to do these studies like never before. We can zoom in on microbial products.”
The work is scientifically sound, said Dr William Busse, a professor of allergy, pulmonary and critical care medicine at the University of Wisconsin. “It is an extremely positive march forward,” he said. “This is an exciting paper.”
Now, said Dr Talal Chatila, an immunologist at Harvard Medical School, “it is not far-fetched to start thinking of how one could harness those bacteria for a therapeutic intervention.”
Chatila, who wrote an editorial accompanying the new paper, hastened to add that he was not suggesting that people start packaging Amish dust and selling it in pharmacies to protect children from asthma. But, he said, “I wouldn’t be surprised if inactive forms of the bacteria could be used.” — The New York Times